Electrochemical Difluoromethylation:New Reagent And New Reactions

The difluoromethyl group(CF2H)can serve as a hydrogen-bonding donor and a lipophilic isostere in drug design for functionalities such as amide,alcohol,thiol and hydroxamic acid.Fluorinated alkyl radicals are reactive towards ? system,which makes radical fluoroalkylation potentially broadly applicable.Compared to the plethora of literatures on trifluoromethylation,there have only been a few published studies on the development of radical difiuoromethylation reactions,possibly because CF2H radical is more difficult to produce and also less reactive than CF3 radical.Recently,the development of new difluoromethyl radical methods-based difluoromethylation reagent has gained much attention.This dissertation is divided into the following sections mainly:In the first part,a air-stable and solid difluoromethlation reagent(CF2HSO2NHNHBoc)can be prepared in one step from commercially available reagents CF2HSO2Cl and NH2NHBoc.The CF2H radical,generated through electrochemical oxidation or ferrocene-mediated electrochemical oxidation,participates in an alkene radical cycloaddition and difunctionalization reaction.In the second part,The CFZH radical,generated through ferrocene-mediated electrochemical oxidation with CF2HSO2NHNHBoc(DFMH),participates in an unexplored alkyne addition reaction followed by a challenging 7-membered ring-forming homolytic aromatic substitution step to afford fluorinated dibenzazepines.In the third part,Electrochemical 1,2-hydroxydifluoromethylation and C-H difluoromethylation of acrylamides were developed by using DFMH as the source of the CF2H group.These electricity-powered oxidative alkene functionalization reactions do not need transition-metal catalysts or chemieal oxidants.The reaction outcome,1,2-difuntionalization or C-H functionalization,is determined by the substituents on the amide nitrogen atom of the acrylamides instead of by the reaction conditions.